Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease

Autores
Taravini, Irene Rita Eloisa; Larramendy, Celia; Gomez, Gimena; Saborido, Mariano Diego; Spaans, Floor; Fresno Rodríguez, Cristóbal; González, Germán A.; Fernandez, Elmer Andres; Murer, Mario Gustavo; Gershanik, Oscar Samuel
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Whether the treatment of Parkinson's disease has to be initiated with levodopa or a D2 agonist like pramipexole remains debatable. Levodopa is more potent against symptoms than D2 agonists, but D2 agonists are less prone to induce motor complications and may have neuroprotective effects. Although regulation of plastic changes in striatal circuits may be the key to their different therapeutic potential, the gene expression patterns induced by de novo treatments with levodopa or D2 agonists are currently unknown. By studying the whole striatal transcriptome in a rodent model of early stage Parkinson's disease, we have identified the gene expression patterns underlying therapeutically comparable chronic treatments with levodopa or pramipexole. Despite the overall relatively small size of mRNA expression changes at the level of individual transcripts, our data show a robust and complete segregation of the transcript expression patterns induced by both treatments. Moreover, transcripts related to oxidative metabolism and mitochondrial function were enriched in levodopa-treated compared to vehicle-treated and pramipexole-treated animals, whereas transcripts related to olfactory transduction pathways were enriched in both treatment groups compared to vehicle-treated animals. Thus, our data reveal the plasticity of genetic striatal networks possibly contributing to the therapeutic effects of the most common initial treatments for Parkinson's disease, suggesting a role for oxidative stress in the long term complications induced by levodopa and identifying previously overlooked signaling cascades as potentially new therapeutic targets.
Fil: Taravini, Irene Rita Eloisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Larramendy, Celia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Gomez, Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Saborido, Mariano Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Spaans, Floor. University of Groningen; Países Bajos
Fil: Fresno Rodríguez, Cristóbal. Area de Cs. Agrarias, Ingeniería, Cs. Biológicas y de la Salud de la Universidad Catolica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: González, Germán A.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Area de Cs. Agrarias, Ingeniería, Cs. Biológicas y de la Salud de la Universidad Catolica de Córdoba; Argentina
Fil: Fernandez, Elmer Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Area de Cs. Agrarias, Ingeniería, Cs. Biológicas y de la Salud de la Universidad Catolica de Córdoba; Argentina
Fil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Gershanik, Oscar Samuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Materia
Differential Transcript Expression Patterns
Levodopa
Parkinson'S Disease
Pramipexole
Striatum
Transcriptome
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/50297
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's diseaseTaravini, Irene Rita EloisaLarramendy, CeliaGomez, GimenaSaborido, Mariano DiegoSpaans, FloorFresno Rodríguez, CristóbalGonzález, Germán A.Fernandez, Elmer AndresMurer, Mario GustavoGershanik, Oscar SamuelDifferential Transcript Expression PatternsLevodopaParkinson'S DiseasePramipexoleStriatumTranscriptomehttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Whether the treatment of Parkinson's disease has to be initiated with levodopa or a D2 agonist like pramipexole remains debatable. Levodopa is more potent against symptoms than D2 agonists, but D2 agonists are less prone to induce motor complications and may have neuroprotective effects. Although regulation of plastic changes in striatal circuits may be the key to their different therapeutic potential, the gene expression patterns induced by de novo treatments with levodopa or D2 agonists are currently unknown. By studying the whole striatal transcriptome in a rodent model of early stage Parkinson's disease, we have identified the gene expression patterns underlying therapeutically comparable chronic treatments with levodopa or pramipexole. Despite the overall relatively small size of mRNA expression changes at the level of individual transcripts, our data show a robust and complete segregation of the transcript expression patterns induced by both treatments. Moreover, transcripts related to oxidative metabolism and mitochondrial function were enriched in levodopa-treated compared to vehicle-treated and pramipexole-treated animals, whereas transcripts related to olfactory transduction pathways were enriched in both treatment groups compared to vehicle-treated animals. Thus, our data reveal the plasticity of genetic striatal networks possibly contributing to the therapeutic effects of the most common initial treatments for Parkinson's disease, suggesting a role for oxidative stress in the long term complications induced by levodopa and identifying previously overlooked signaling cascades as potentially new therapeutic targets.Fil: Taravini, Irene Rita Eloisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Larramendy, Celia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Gomez, Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Saborido, Mariano Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Spaans, Floor. University of Groningen; Países BajosFil: Fresno Rodríguez, Cristóbal. Area de Cs. Agrarias, Ingeniería, Cs. Biológicas y de la Salud de la Universidad Catolica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: González, Germán A.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Area de Cs. Agrarias, Ingeniería, Cs. Biológicas y de la Salud de la Universidad Catolica de Córdoba; ArgentinaFil: Fernandez, Elmer Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Area de Cs. Agrarias, Ingeniería, Cs. Biológicas y de la Salud de la Universidad Catolica de Córdoba; ArgentinaFil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Gershanik, Oscar Samuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaPergamon-Elsevier Science Ltd2015-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/50297Taravini, Irene Rita Eloisa; Larramendy, Celia; Gomez, Gimena; Saborido, Mariano Diego; Spaans, Floor; et al.; Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease; Pergamon-Elsevier Science Ltd; Neuropharmacology; 101; 5-2015; 576-5890028-3908CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0028390815001471info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuropharm.2015.04.018info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:45:06Zoai:ri.conicet.gov.ar:11336/50297instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:45:06.463CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease
title Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease
spellingShingle Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease
Taravini, Irene Rita Eloisa
Differential Transcript Expression Patterns
Levodopa
Parkinson'S Disease
Pramipexole
Striatum
Transcriptome
title_short Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease
title_full Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease
title_fullStr Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease
title_full_unstemmed Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease
title_sort Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease
dc.creator.none.fl_str_mv Taravini, Irene Rita Eloisa
Larramendy, Celia
Gomez, Gimena
Saborido, Mariano Diego
Spaans, Floor
Fresno Rodríguez, Cristóbal
González, Germán A.
Fernandez, Elmer Andres
Murer, Mario Gustavo
Gershanik, Oscar Samuel
author Taravini, Irene Rita Eloisa
author_facet Taravini, Irene Rita Eloisa
Larramendy, Celia
Gomez, Gimena
Saborido, Mariano Diego
Spaans, Floor
Fresno Rodríguez, Cristóbal
González, Germán A.
Fernandez, Elmer Andres
Murer, Mario Gustavo
Gershanik, Oscar Samuel
author_role author
author2 Larramendy, Celia
Gomez, Gimena
Saborido, Mariano Diego
Spaans, Floor
Fresno Rodríguez, Cristóbal
González, Germán A.
Fernandez, Elmer Andres
Murer, Mario Gustavo
Gershanik, Oscar Samuel
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Differential Transcript Expression Patterns
Levodopa
Parkinson'S Disease
Pramipexole
Striatum
Transcriptome
topic Differential Transcript Expression Patterns
Levodopa
Parkinson'S Disease
Pramipexole
Striatum
Transcriptome
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Whether the treatment of Parkinson's disease has to be initiated with levodopa or a D2 agonist like pramipexole remains debatable. Levodopa is more potent against symptoms than D2 agonists, but D2 agonists are less prone to induce motor complications and may have neuroprotective effects. Although regulation of plastic changes in striatal circuits may be the key to their different therapeutic potential, the gene expression patterns induced by de novo treatments with levodopa or D2 agonists are currently unknown. By studying the whole striatal transcriptome in a rodent model of early stage Parkinson's disease, we have identified the gene expression patterns underlying therapeutically comparable chronic treatments with levodopa or pramipexole. Despite the overall relatively small size of mRNA expression changes at the level of individual transcripts, our data show a robust and complete segregation of the transcript expression patterns induced by both treatments. Moreover, transcripts related to oxidative metabolism and mitochondrial function were enriched in levodopa-treated compared to vehicle-treated and pramipexole-treated animals, whereas transcripts related to olfactory transduction pathways were enriched in both treatment groups compared to vehicle-treated animals. Thus, our data reveal the plasticity of genetic striatal networks possibly contributing to the therapeutic effects of the most common initial treatments for Parkinson's disease, suggesting a role for oxidative stress in the long term complications induced by levodopa and identifying previously overlooked signaling cascades as potentially new therapeutic targets.
Fil: Taravini, Irene Rita Eloisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Larramendy, Celia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Gomez, Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Saborido, Mariano Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Spaans, Floor. University of Groningen; Países Bajos
Fil: Fresno Rodríguez, Cristóbal. Area de Cs. Agrarias, Ingeniería, Cs. Biológicas y de la Salud de la Universidad Catolica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: González, Germán A.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Area de Cs. Agrarias, Ingeniería, Cs. Biológicas y de la Salud de la Universidad Catolica de Córdoba; Argentina
Fil: Fernandez, Elmer Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Area de Cs. Agrarias, Ingeniería, Cs. Biológicas y de la Salud de la Universidad Catolica de Córdoba; Argentina
Fil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Gershanik, Oscar Samuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
description Whether the treatment of Parkinson's disease has to be initiated with levodopa or a D2 agonist like pramipexole remains debatable. Levodopa is more potent against symptoms than D2 agonists, but D2 agonists are less prone to induce motor complications and may have neuroprotective effects. Although regulation of plastic changes in striatal circuits may be the key to their different therapeutic potential, the gene expression patterns induced by de novo treatments with levodopa or D2 agonists are currently unknown. By studying the whole striatal transcriptome in a rodent model of early stage Parkinson's disease, we have identified the gene expression patterns underlying therapeutically comparable chronic treatments with levodopa or pramipexole. Despite the overall relatively small size of mRNA expression changes at the level of individual transcripts, our data show a robust and complete segregation of the transcript expression patterns induced by both treatments. Moreover, transcripts related to oxidative metabolism and mitochondrial function were enriched in levodopa-treated compared to vehicle-treated and pramipexole-treated animals, whereas transcripts related to olfactory transduction pathways were enriched in both treatment groups compared to vehicle-treated animals. Thus, our data reveal the plasticity of genetic striatal networks possibly contributing to the therapeutic effects of the most common initial treatments for Parkinson's disease, suggesting a role for oxidative stress in the long term complications induced by levodopa and identifying previously overlooked signaling cascades as potentially new therapeutic targets.
publishDate 2015
dc.date.none.fl_str_mv 2015-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/50297
Taravini, Irene Rita Eloisa; Larramendy, Celia; Gomez, Gimena; Saborido, Mariano Diego; Spaans, Floor; et al.; Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease; Pergamon-Elsevier Science Ltd; Neuropharmacology; 101; 5-2015; 576-589
0028-3908
CONICET Digital
CONICET
url http://hdl.handle.net/11336/50297
identifier_str_mv Taravini, Irene Rita Eloisa; Larramendy, Celia; Gomez, Gimena; Saborido, Mariano Diego; Spaans, Floor; et al.; Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease; Pergamon-Elsevier Science Ltd; Neuropharmacology; 101; 5-2015; 576-589
0028-3908
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0028390815001471
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuropharm.2015.04.018
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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